title: A pineal regulatory element (PIRE) mediates transactivation by the pineal/retina-specific transcription factor CRX.
abstract: The circadian hormone melatonin is synthesized predominantly in the pineal gland by the actions of two pineal-specific enzymes: serotonin N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT). Pineal night-specific ATPase (PINA), another pineal- and night-specific protein we recently identified, is produced as a truncated form of the Wilson disease gene (Atp7b) product. To identify the regulatory elements required for pineal-specific gene expression, we isolated sequences upstream of the rat PINA gene and discovered a cis-acting element that is recognized by a novel pineal/retina-specific nuclear factor. This pineal regulatory element (PIRE) has a consensus of TAATC/T and is present in six copies in the 5' regulatory region of the PINA gene, at least three copies in the rat NAT promoter, and at least one copy in each of the putative HIOMT promoters A and B. A recently identified retina-specific protein, cone rod homeobox (CRX), binds to PIRE in vitro and transactivates PIRE-reporter constructs. These data suggest that Crx may play a crucial role in regulating pineal gene expression through interactions with PIRE.
authors.affiliation: Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.forename: D J
authors.initials: DJ
authors.lastname: Zack
authors.forename: S H
authors.initials: SH
authors.lastname: Snyder
authors.forename: J
authors.initials: J
authors.lastname: Borjigin
mesh_terms: D000121:Acetylserotonin O-Methyltransferase / Q000235:genetics; D000251:Adenosine Triphosphatases / Q000235:genetics*; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D027682:Cation Transport Proteins; D002940:Circadian Rhythm; D000073840:Copper-Transporting ATPases; D004268:DNA-Binding Proteins / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D018398:Homeodomain Proteins / Q000502:physiology*; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D010870:Pineal Gland / Q000502:physiology*; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D012045:Regulatory Sequences, Nucleic Acid; D012160:Retina / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D015534:Trans-Activators; C109288:cone rod homeobox protein; D000121:Acetylserotonin O-Methyltransferase; D001191:Arylamine N-Acetyltransferase; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases